Despite widespread availability of safe and effective COVID-19 vaccines in the US, only about 66% of the eligible US population had taken the recommended initial doses of the COVID-19 vaccines as of April 2022. Explanations for this hesitancy have focused on misinformation about the vaccines, lack of trust in health authorities, and acceptance of conspiracy theories about the pandemic. Here we test whether those with a conspiratorial mindset, which distrusts a wide range of institutions, were poised to reject COVID vaccines before the pandemic even began. To answer that question, we reinterviewed members of a national US panel that we had previously surveyed beginning in 2018. As hypothesized, having a conspiratorial mindset in 2019 predicted COVID-vaccination hesitancy in 2021 better than prior trust in health authorities or acceptance of vaccine misinformation. Those with the mindset were also more likely to consume media that bolstered belief in pandemic conspiracies. Research is needed on the determinants of conspiratorial mindset and ways to minimize the likelihood that consequential health decisions will be influenced by it.